Cellular and Molecular Life Sciences

, Volume 69, Issue 9, pp 1447–1473

Eukaryotic DNA damage checkpoint activation in response to double-strand breaks

Review

Abstract

Double-strand breaks (DSBs) are the most detrimental form of DNA damage. Failure to repair these cytotoxic lesions can result in genome rearrangements conducive to the development of many diseases, including cancer. The DNA damage response (DDR) ensures the rapid detection and repair of DSBs in order to maintain genome integrity. Central to the DDR are the DNA damage checkpoints. When activated by DNA damage, these sophisticated surveillance mechanisms induce transient cell cycle arrests, allowing sufficient time for DNA repair. Since the term “checkpoint” was coined over 20 years ago, our understanding of the molecular mechanisms governing the DNA damage checkpoint has advanced significantly. These pathways are highly conserved from yeast to humans. Thus, significant findings in yeast may be extrapolated to vertebrates, greatly facilitating the molecular dissection of these complex regulatory networks. This review focuses on the cellular response to DSBs in Saccharomyces cerevisiae, providing a comprehensive overview of how these signalling pathways function to orchestrate the cellular response to DNA damage and preserve genome stability in eukaryotic cells.

Keywords

Cancer Checkpoint DNA damage Double-strand break Yeast Genome instability 

Abbreviations

ATM

Ataxia telangiectasia mutated

ATR

ATM and Rad3-related

ATRIP

ATR interacting protein

BRCT

BRCA1 carboxyl terminal

CAD

Chk1 activation domain

CDK

Cyclin-dependent kinase

DDK

Dbf4-dependent kinase

DDR

DNA damage response

DNA-PKcs

DNA-dependent protein kinase catalytic subunit

DSB

Double-strand break

GCRs

Gross chromosomal rearrangements

G1

Gap phase 1

G2

Gap phase 2

HR

Homologous recombination

IR

Ionising radiation

M

Mitosis

MEN

Mitotic exit network

MMS

Methyl methanesulfonate

MRX/MRN

Mre11-Rad50-Xrs2/MRE11-RAD50-NBS1

NHEJ

Non-homologous end joining

PIKK

Phosphoinositide 3-kinase related kinase

PTM

Post-translational modification

RNR

Ribonucleotide reductase

RPA

Replication protein A

SCD

SQ/TQ cluster domain

UV

Ultraviolet

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© Springer Basel AG 2011

Authors and Affiliations

  1. 1.Genome Stability Laboratory, Centre for Chromosome Biology, School of Natural SciencesNational University of Ireland GalwayGalwayIreland

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